Page 760 - Withrow and MacEwen's Small Animal Clinical Oncology, 6th Edition

738 PART IV Specific Malignancies in the Small Animal Patient

sometimes appears disorderly, and there may be variation in the morphology (especially shape), and leukoerythroblastosis. Bone
size and shape of neutrophils at the same level of maturation. In marrow aspiration is usually unsuccessful, resulting in a “dry tap.”
This necessitates a bone marrow biopsy obtained with a Jamshidi
addition, neoplastic leukocytes may disintegrate more rapidly and
VetBooks.ir appear vacuolated. 697 Because of the invasive nature of CML, needle. 740 The specimen is processed for routine histopathologic
examination and, if necessary, special stains for fibrous tissue can
biopsy of liver or spleen may also help distinguish true leukemia
from a leukemoid reaction, assuming the animal can tolerate the be used. Because myelofibrosis occurs secondary to other dis-
procedure. Fluorescent in situ hybridization analysis is available eases of bone marrow, such as chronic hemolytic anemia or bone
to identify chromosomal rearrangements, including translocations marrow necrosis, the clinician should look for a primary disease
(e.g., Raleigh chromosome), inversions, and deletions, in dogs; process.
some of these aberrations are associated with certain forms of leu- The concept of clinical staging of patients with AML, MPD,
kemia, and continued investigations will likely yield a larger data- and MDS is obviously much different than that of patients with
base of cytogenetic abnormalities and their links to hematologic solid tumors. As these hematologic tumors are “liquid,” that is
malignancies. 614,624–630,678,679,681,699–702 they involve primarily the peripheral blood and bone marrow
Basophilic leukemia is diagnosed by finding excessive num- compartments, clinical staging is generally not performed beyond
bers of basophils in circulation and in bone marrow. Basophilic these two compartments. Certainly, infiltration of peripheral
leukemia must be differentiated from mastocytosis based on the nodes and other organs occurs; however, documentation of their
morphology of the cell type present. Basophils have a segmented involvement with advanced imaging or tissue aspirates does not
“ribbon-like” nucleus and variably sized granules, whereas mast alter treatment or prognosis in any significant way. Two studies
cells have a round-to-oval nucleus that may be partially or totally have documented the proof-of-concept use of 3-T body MRI to
obscured by small, round, metachromatic-staining granules. This distinguish diffuse versus focal bone marrow and/or parenchymal
distinction is usually easy to make; however, in basophilic leuke- involvement of hematopoetic neoplasia; however, the clinical util-
mia, changes in the morphology of the nucleus and granules make ity of this methodology is currently unknown. 741,742
the distinction less clear. 706
ET has been diagnosed based on finding persistent and exces- Treatment
sive thrombocytosis (>600,000/μL) without circulating blast cells
and in the absence of another MPD (e.g., PV), myelofibrosis, or Acute Myeloid Leukemia
disorders known to cause secondary thrombocytosis, 710 includ- Treatment of acute nonlymphocytic leukemias has been unre-
ing iron deficiency anemia, chronic inflammatory diseases, recov- warding to date. There is limited information on the response
ery from severe hemorrhage, rebound from immune-mediated of specific subtypes of leukemia to uniform chemotherapeutic
thrombocytopenia, and absence of a spleen. Thrombocytosis is protocols, in part owing to the rarity of these diseases and the
transient in these disorders or abates with resolution of the pri- paucity of cases in the literature. Veterinarians are advised to
mary disease. In ET, platelet morphology may be abnormal with contact a veterinary oncologist for discussion of new protocols
bizarre giant forms and abnormal granulation. 713 In the bone and appropriate management of these cases, as novel agents
marrow, megakaryocytic hyperplasia is a consistent feature and are currently in development and may become available in the
dysplastic changes may be evident in megakaryocytes. 712 Spurious future.
hyperkalemia may be present in serum samples from dogs with The overriding therapeutic goal is to eradicate leukemic cells
thrombocytosis from any cause due to the release of potassium and reestablish normal hematopoiesis. Currently, this is best
from platelets during clot formation. 738 Measuring potassium in accomplished by cytoreductive chemotherapy and the agents most
plasma is recommended in these cases and usually demonstrates a commonly utilized include combinations of anthracyclines, such
potassium concentration within reference interval. Platelet aggre- as doxorubicin, cyclophosphamide, vincristine, 6-thioguanine,
gability has been variably reported as impaired 713 or enhanced. 712 and prednisone. 618–620,640,644,646,707,743–746 In dogs, cytosine arabi-
In the one dog in which it was measured, plasma thrombopoietin noside (Ara-C), 100 to 200 mg/m , given by slow infusion (12–24
2
(TPO) concentration was normal. 711 It is unclear whether TPO hours) daily for 3 days and repeated weekly, has been used, as well
plays a role in ET or is suppressed by the high platelet mass. as several other variations using subcutaneous injections of Ara-C
In MDS, abnormalities in two or three cell lines are usually (see Chapter 12). Several variations of CHOP- or COP-based
manifested in peripheral blood as neutropenia with or without a left protocols (see Section A of this chapter), with or without Ara-C,
shift, nonregenerative anemia, or thrombocytopenia. Other changes have been used as well. The overall prognosis with currently avail-
include macrocytosis and metarubricytosis. The bone marrow is typi- able treatment is poor. Although response rates to multiagent pro-
cally normocellular or hypercellular with an increased M : E ratio, and tocols are relatively high (50%–70%), responses are not durable
blasts cells, although increased, constitute less than 20% of nucleated and MSTs, despite aggressive protocols, are generally 0.5 to 2.0
cells; in a report of 13 dogs with primary or secondary MDS, in all months. 618–620 Obviously, effective therapies for AML in dogs
but one dog the blast cell percentage was less than 20%. 739 Dys- await further investigation.
plastic changes can be detected in any cell line. Dyserythropoiesis is Regardless of the chemotherapy protocol used, significant cyto-
characterized by asynchronous maturation of erythroid cells typified penias either persist or are sequela to chemotherapy, and intensive
by large hemoglobinized cells with immature nuclei (megaloblastic supportive care will be necessary. Transfusions of whole blood or
change). If the erythroid component is dominant, the MDS is called platelet-rich plasma may be required to treat anemia and throm-
MDS-Er (see Table 33.13). 615,638 In dysgranulopoiesis, giant neu- bocytopenia, and infection should be managed with aggressive
trophil precursors and abnormalities in nuclear segmentation and antibiotic therapy. Because of the generally poor response, many
cytoplasmic granulation can be seen. Finally, dysthrombopoiesis is clients will choose palliative supportive care; however, the acute
characterized by giant platelets and micromegakaryocytes. progression of disease does not allow for prolonged palliation in
Myelofibrosis should be suspected in animals with nonregen- most cases and MSTs with supportive care are generally only 1 to
erative anemia or pancytopenia, abnormalities in erythrocyte 2 weeks.